[A 28-day repeated dose toxicity study of nitrobenzene in F344 rats].

To examine toxicities of nitrobenzene as part of the re-evaluation of toxicities of existing chemicals, a 28-day repeat dose toxicity study was performed in male and female F344 rats at dosages of 0, 5, 25 and 125 mg/kg/day of nitrobenzene. All rats in each group consisting of 6 males and 6 females received a daily intragastric administration of this chemical for 28 days. Additional two groups of animals exposed to 0 and 125 mg/kg/day were used for examinations of subsequent recovery for 2 weeks. One female in the 125 mg/kg group died on day 27. Decreased movement, pale skin, gait abnormality and decreases of body weights or their gains were seen in the 125 mg/kg group. Hematology revealed decreases of RBC, Hb and Ht in the 25 and/or 125 mg/kg groups. Blood biochemistry revealed increases of total cholesterol and albumin and decreases of BUN in the 25 and 125 mg/kg groups, and increases of A/G ratio in both sexes and ALT, ALP and total protein in females in the 125 mg/kg group. In the organ weight, increases of the liver, spleen, kidney weight and decreases of the testis and thymus were seen in the 125 mg/kg group. In addition, the increased liver weight was also seen in males receiving 5 mg/kg, and the increased spleen weight in both sexes receiving 25 mg/kg. Histopathology revealed spongiotic changes and brown pigmentation in perivascular region of the cerebellum, increased extramedullary hematopoiesis of the liver, brown pigmentation of renal tubular epithelium and degeneration of seminiferous tubular epithelium and atrophy of seminiferous tubule in the 125 mg/kg group, and congestion, increased brown pigmentation in red pulp and increased extramedullary hematopoiesis of the spleen and increased hematopoiesis of the bone marrow in treated groups. Findings mentioned above disappeared or tended to be decreased during or at the end of the recovery period. Although no effect-dose level was detected in this study, severe anemia and disorder of spermatogenesis and central nervous system which have been reported in the long-term toxicity study could be reconfirmed.